TY - JOUR
T1 - Combination of miR-143 and miR-506 reduces lung and pancreatic cancer cell growth through the downregulation of cyclin-dependent kinases
AU - Hossian, A. K.M.Nawshad
AU - MacKenzie, Gerardo G.
AU - Mattheolabakis, George
N1 - Funding Information:
This work was supported by the College of Pharmacy, University of Louisiana Monroe start‑up funding, and the National Institutes of Health (NIH) through the National Institute of General Medical Science Grants 5 P20 GM103424‑15, 3 P20 GM103424‑15S1.
PY - 2021/4
Y1 - 2021/4
N2 - Lung cancer (LC) and pancreatic cancer (PC) are the first and fourth leading causes of cancer-related deaths in the US. Deregulated cell cycle progression is the cornerstone for rapid cell proliferation, tumor development, and progression. Here, we provide evidence that a novel combinatorial miR treatment inhibits cell cycle progression at two phase transitions, through their activity on the CDK4 and CDK1 genes. Following transfection with miR-143 and miR-506, we analyzed the differential gene expression of CDK4 and CDK1, using qPCR or western blot analysis, and evaluated cell cycle inhibition, apoptosis and cytotoxicity. The combinatorial miR-143/506 treatment downregulated CDK4 and CDK1 levels, and induced apoptosis in LC cells, while sparing normal lung fibroblasts. Moreover, the combinatorial miR treatment demonstrated a comparable activity to clinically tested cell cycle inhibitors in inhibiting cell cycle progression, by presenting substantial inhibition at the G1/S and G2/M cell cycle transitions. More importantly, the miR-143/506 treatment presented a broader application, effectively downregulating CDK1 and CDK4 levels, and reducing cell growth in PC cells. These findings suggest that the miR-143/506 combination acts as a promising approach to inhibit cell cycle progression for cancer treatment with minimal toxicity to normal cells.
AB - Lung cancer (LC) and pancreatic cancer (PC) are the first and fourth leading causes of cancer-related deaths in the US. Deregulated cell cycle progression is the cornerstone for rapid cell proliferation, tumor development, and progression. Here, we provide evidence that a novel combinatorial miR treatment inhibits cell cycle progression at two phase transitions, through their activity on the CDK4 and CDK1 genes. Following transfection with miR-143 and miR-506, we analyzed the differential gene expression of CDK4 and CDK1, using qPCR or western blot analysis, and evaluated cell cycle inhibition, apoptosis and cytotoxicity. The combinatorial miR-143/506 treatment downregulated CDK4 and CDK1 levels, and induced apoptosis in LC cells, while sparing normal lung fibroblasts. Moreover, the combinatorial miR treatment demonstrated a comparable activity to clinically tested cell cycle inhibitors in inhibiting cell cycle progression, by presenting substantial inhibition at the G1/S and G2/M cell cycle transitions. More importantly, the miR-143/506 treatment presented a broader application, effectively downregulating CDK1 and CDK4 levels, and reducing cell growth in PC cells. These findings suggest that the miR-143/506 combination acts as a promising approach to inhibit cell cycle progression for cancer treatment with minimal toxicity to normal cells.
KW - Cell cycle
KW - Lung cancer
KW - MiR-143
KW - MiR-506
KW - Pancreatic cancer
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U2 - 10.3892/or.2021.7953
DO - 10.3892/or.2021.7953
M3 - Article
C2 - 33649787
AN - SCOPUS:85100603787
VL - 45
JO - Oncology Reports
JF - Oncology Reports
SN - 1021-335X
IS - 4
M1 - 7953
ER -